Although hypertensive crisis, status epilepticus, and accidental deaths (e.g., drowning) have been implicated, respiratory arrest is probably the most frequent cause of deaths that have accompanied the increased abuse of phencyclidine (PCP). Antidotes are available to help manage the hypertensive, convulsive and psychotic reactions seen in PCP overdosage, but none has been found for the respiratory depression. The initial objective of this study is to characterize the respiratory depressant actions of PCP with respect to stages of development. Subsequent identification of its sites and mechanisms of action should provide leads to the development of effective antidotes. Possible potentiation of PCP-induced respiratory depression by drugs commonly coadministered with PCP (e.g., THC, cocaine, CPZ, diazepam) will also be assessed. The results of these animal studies should provide a sound basis for the most effective management of this important and sometimes lethal respiratory manifestation of overdosage with PCP-type drugs of abuse.